Mast Cell Activation Disease and Microbiotic Interactions

Mast cell (MC) disease has long been thought to be just the rare disease of mastocytosis (in various forms, principally cutaneous and systemic), with aberrant MC mediator release at symptomatic levels due to neoplastic MC proliferation. Recent discoveries now show a new view is in order, with mastocytosis capping a metaphorical iceberg now called "MC activation disease" (MCAD, i.e. disease principally manifesting inappropriate MC activation), with the bulk of the iceberg being the recently recognized "MC activation syndrome" (MCAS), featuring inappropriate MC activation to symptomatic levels with little to no inappropriate MC proliferation. Given increasing appreciation of a great menagerie of mutations in MC regulatory elements in mastocytosis and MCAS, the great heterogeneity of MCAD's clinical presentation is unsurprising. Most MCAD patients present with decades of chronic multisystem polymorbidity generally of an inflammatory ± allergic theme. Preliminary epidemiologic investigation suggests MCAD, while often misrecognized, may be substantially prevalent, making it increasingly important that practitioners of all stripes learn how to recognize its more common forms such as MCAS. We review the diagnostically challenging presentation of MCAD (with an emphasis on MCAS) and current thoughts regarding its biology, epidemiology, natural history, diagnostic evaluation, and treatment.

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“…11,31,33). Lifestyleassociated factors (diet, intestinal microbiome, alcohol) may influence MCAD phenotype (34,35).…”

Section: Systemmentioning

confidence: 98%

“…Mefloquine was recently found to induce MC apoptosis in vitro (72). Interactions between MCs and the intestinal microbiome, and related therapeutic opportunities, warrant investigation (35). Next-generation sequencing and genome-wide association studies may facilitate identification of disease-related operator and/or regulator genes.…”

Section: Future Developmentmentioning

confidence: 99%

Often seen, rarely recognized: mast cell activation disease – a guide to diagnosis and therapeutic options

et al. 2016

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“…[12] Mast cells are effector cells of the immune system, found principally in all organs and vascularized tissues which are in contact with the outer environment [16] and regulate adaptive and innate immunity. [16,17] Mast cells could be seen in the skin, the gastrointestinal and the respiratory tracts, and also found in the peritoneum and synovium. [16] They are highly active cells of hypersensitivity reactions and allergic disorders, as seen in the allergic or parasitic inflammations.…”

Section: Discussionmentioning

confidence: 99%

Effects of chronic unpredictable stress on intestinal morphology in Wistar rats

Çorumlu¹,

Aydin²,

Ulupinar³

2019

Anatomy

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Objectives: Stressful events might cause immune dysfunction and trigger various disorders. Adverse effects of acute or chronic stress exposure on the gastrointestinal system have been shown previously in several studies. In this experimental study, we used chronic unpredictable stress (CUS) paradigm to better mimic effects of the intermittent exposure to daily life stress and investigated the morphometric alterations occurring in the small intestines of rats. Methods: Male Wistar rats were randomly divided into stress and control groups (n=8, each). While stress group was subjected to chronic unpredictable stress protocol for 21 days, control group remained undisturbed. Intestinal tissue samples were obtained from two different regions; one was 3-6 cm away from the pylorus and the other one 3-6 cm prior to the ileocaecal valve. Tissue sections were obtained from paraffin blocks at the thickness of 3 micrometers and stained with hematoxylin-eosin (HE) or periodic acid-Shiff (PAS). The lengths of villi were measured from the basal membrane to the top of the villus. The ratio of degranulating and non-degranulating mast cells per unit area were estimated by point counting method. Results: The mean villi length in the stress group were significantly higher (p<0.01) than those of the control group. Degranulation to non-degranulation ratio of the mast cells were 40% and 54% in the control and stress groups, respectively. Conclusion: Animals exposed to chronic unpredictable stress protocol displayed a significant elongation in the villi of small intestines and an increase in the number of degranulating mast cells in the intestinal mucosa. Since activation of mast cells causes releasing of various chemical mediators and growth factors, it is plausible that stressed animals developed an adaptation mechanism to enhance the capacity for absorption and digestion per unit length of the guts.

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“…Although roles of MCs in the host-microbiome relationship have been well described, mainly in gut microbiomes [10–13], in this review we focus on the role of MCs in the skin and microbiomes of the skin, which have unique and different characteristics and functions from gut microbiomes [14, 15]. …”

Section: Introductionmentioning

confidence: 99%